Palladium‐Mediated Annulation of Vinyl Aziridines with Michael Acceptors: Stereocontrolled Synthesis of Substituted Pyrrolidines and Its Application in a Formal Synthesis of (−)‐α‐Kainic Acid

Abstract

Just add salt: Vinyl aziridines have been treated with methyl vinyl ketone or ethyl thioacrylate in the presence of Pd0 to give pyrrolidines with moderate to good diastereoselectivity. The presence of nBu4NCl was critical to successful annulation. The synthetic utility of the methodology has been demonstrated in a short (formal) synthesis of (−)‐α‐kainic acid.

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…Then β-H elimination of these intermediates produces intermediate 376, which undergoes reductive elimination to afford an N-tosylenamine. 299 Isomerization of the N-tosylenamine forms 373.…”

Transition metal-catalyzed allylic substitution reactions with unactivated allylic substrates

“…89 Regioselectivity can be explained via the possible formation of a 5-membered transition state (Scheme 58). 90 Aziridines 82 could be reacted with Michael acceptors 83 in the presence of Pd 2 (dba) 3 ÁCHCl 3 , Scheme 53 Pd(0)-catalyzed 3-aza-Cope rearrangement of N-allylenamines. Nucleophilic attack therefore proceeds through the favored five-membered transition state 78 giving the branched product 79.…”

“…90 The phenyl group adopts a pseudoaxial position to minimize steric hindrance with the PdL n complex. 90 The phenyl group adopts a pseudoaxial position to minimize steric hindrance with the PdL n complex.…”

Recent applications of aziridine ring expansion reactions in heterocyclic synthesis

“…Lowe and coworkers have reported the reaction of trans-3-styryl-2-phenyl-Ntosylaziridines 88 with methyl vinyl ketone (X = Me) or with ethyl thioacrylate (X = SEt) 89 in the presence of a palladium catalyst, a phosphine and an additive to give a diastereomeric mixture of pyrrolidines 90a-d in 60-66% yields with excellent enantioselectivity (ee 92-93%) (Scheme 28). 65 The reaction was promoted by nonpolar solvents -pentane, diethyl ether or mixtures of diethyl ether/pentane, and sterically hindered phosphines; (o-tol) 3 P, (2-furyl) 3 P and (4-F-Ph) 3 P. The presence of a styryl group on C-2 position of the aziridine furnished excellent diastereoselectivities but moderate yields. Replacing the styryl group with a 4-chlorophenyl group or 1-propenyl group lowered both the diastereoselectivity and yield.…”

“…65 Aziridine 91 also reacted with ethyl thioacrylate 89 to give the diastereomer 92a as the major product (Scheme 29). …”